Elevated Plasma Homocysteine Level in Patients With Parkinson Disease

Abstract

Background: An elevated plasma homocysteine (Hcy) level has been prospectively associated with an increased risk of vascular and degenerative dementias. An Hcy elevation is prevalent in patients with Parkinson disease (PD) in part because levodopa metabolism produces Hcy. The clinical relevance of an elevated Hcy level in patients with PD is unknown.Objective: To determine if hyperhomocysteinemia in patients with PD is associated with depression or with cognitive or physical impairments.Design: Ninety-seven people with a mean (SD) PD duration of 3.6 (1.6) years completed the Beck Depression Inventory, a battery of 11 cognitive tests, and the motor and function components of the Unified Parkinson's Disease Rating Scale. Normalized scores for the affective, cognitive, and physical measures were compared between those with a normal Hcy level (n=66) and those with hy-perhomocysteinemia (n = 31) (Hcy level, Ͼ1.89 mg/L [Ͼ14 µmol/L]), controlling for age, sex, disease duration, and treatment.Results: Subjects with an elevated Hcy level were slightly older (68 vs 62 years), but had similar plasma concentrations of vitamin B 12 and folate. Hyperhomocysteinemic patients were more depressed (P=.02) and had worse cognition (PϽ.01), but the physical measure did not differ.Conclusions: Patients with PD and hyperhomocysteinemia are more likely to be depressed and to perform worse on neuropsychometric tasks compared with normohomocysteinemic patients. Further research is warranted to see if hyperhomocysteinemia is a reversible risk factor for neuropsychiatric burden in patients with PD.

Idiopathic Parkinson's Disease, Vascular Risk Factors and Cognition: A Critical Review

“…Only 1/4 studies reported a significant association between the presence of VRF and a decline in the construction praxis. O'Suilleabhain et al (2004; found a significantly worse performance on Block Design (WAIS-III) and on ROCF-copy in the PD group with Hcy>14 μmol/L compared to PD with Hcy < 14 μmol/L at baseline, but not at 2-year follow-up.…”

“…Six studies (Barone et al, 2008-at baseline only); Camicioli et al, 2009;Hassin-Baer et al, 2006;O'Suilleabhain et al, 2004O'Suilleabhain et al, , 2006Ozer et al, 2006;Rodriguez-Oroz et al, 2009) found no association between Hcy and worse global cognition as measured by the MMSE (n=5 studies), the ADAS-Cog (n=1), the BDS (n=1), the DRS (n=1) and the STMS (n=1 study). However, the R-DB-PC study of Barone et al (2008) found that Hcy-rivastigmine-treated patients significantly improved their performance after 24 weeks on the ADAS-Cog and the MMSE compared to Hcy-placebo-treated-patients.…”

“…Moreover, O'Suilleabhain et al (2004O'Suilleabhain et al ( , 2006 found that PD patients with Hcy ≥14 μmol/L compared to those with Hcy <14 μmol/L had significantly lower score on verbal fluency at baseline, but the scores of the 2 groups were comparable at follow-up. However, other studies found no association between Hcy levels and scores of verbal fluency (Hassin-Baer et al, 2006;Ozer et al, 2006;Rodriguez-Oroz et al, 2009) Verbal fluency scores were significantly associated with an increase of intimomedial thickness and of the pulsatility index (Rektor et al, 2009), as well as with coronary HD (Slawek et al, 2008).…”

“…Interestingly, the Hcy studies demonstrated that Hcy may affect episodic memory (O'Suilleabhain et al, 2004(O'Suilleabhain et al, , 2006Ozer et al, 2006), executive functions (Ozer et al, 2006), language (Barone et al, 2008;O'Suilleabhain et al, 2004O'Suilleabhain et al, , 2006, attention/vigilance (Barone et al, 2008), construction praxis (O'Suilleabhain et al, 2004(O'Suilleabhain et al, , 2006 and speed of information processing (Barone et al, 2008). This could reflect a vascular contribution to cognitive impairment since executive functions, attention and some aspects of episodic memory are linked to frontal-subcortical loops (Sachdev et al, 2005).…”

“…For instance, two studies with a longitudinal component (Barone et al,2004;O'Suilleabhain et al, 2004; found a significant association with elevated Hcy and worse cognitive performance, but inconsistencies were found in the casecontrol studies. Thus, an important limitation of the review data concerns the lack of longitudinal and cohort studies on most VRF.…”